Associations between conduct problems in childhood and adverse outcomes in emerging adulthood: a longitudinal Swedish nationwide twin cohort.

BACKGROUND: We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems. METHODS: Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow-up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations. RESULTS: On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (ßboys  = .24, standard error, SE = 0.03; ßgirls  = .17, SE = 0.03), above and beyond its association with the externalizing (ßboys  = 0.21, SE = 0.04; ßgirls  = 0.17, SE = 0.05) and general factors (ßboys  = 0.45, SE = 0.03; ßgirls  = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors. CONCLUSIONS: It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels.

Conduct disorder and somatic health in children: a nationwide genetically sensitive study.

BACKGROUND: Conduct disorder (CD), a serious behavioral and emotional disorder in childhood and adolescence, characterized by disruptive behavior and breaking societal rules. Studies have explored the overlap of CD with neurodevelopmental problems (NDP). The somatic health of children with NDP has been investigated; however, the prevalence of these problems in children with CD has not been sufficiently studied. Holistic assessment of children with CD is required for establishing effective treatment strategies. AIMS: (1) Define the prevalence of selected neurological problems (migraine and epilepsy) and gastrointestinal problems (celiac disease, lactose intolerance, diarrhea, and constipation) in a population of twins aged 9 or 12; (2) Compare the prevalence of somatic problems in three subpopulations: (a) children without CD or NDP, (b) children with CD, and (c) children with both CD and NDP; (3) Select twin pairs where at least one child screened positive for CD but not NDP (proband) and map both children's neurological and gastrointestinal problems. METHOD: Telephone interviews with parents of 20,302 twins in a cross-sectional, nationwide, ongoing study. According to their scores on the Autism-Tics, AD/HD, and Comorbidities inventory, screen-positive children were selected and divided into two groups: (1) children with CD Only, (2) children with CD and at least one NDP. RESULTS: Children with CD had an increased prevalence of each neurological and gastrointestinal problem (except celiac disease), and the prevalence of somatic problems was further increased among children with comorbid CD and NDP. The presence of CD (without NDP) increased the odds of constipation for girls and the odds of epilepsy for boys. Girls with CD generally had more coexisting gastrointestinal problems than boys with CD. Female co-twins of probands with CD were strongly affected by gastrointestinal problems. Concordance analyses suggested genetic background factors in neurological and gastrointestinal problems, but no common etiology with CD could be concluded. CONCLUSION: Co-occurring NDP could explain most of the increased prevalence of somatic problems in CD. Our results raise a new perspective on CD in children and adolescents; their CD seems to be linked to a number of other health problems, ranging from neurodevelopmental and psychiatric disorders to somatic complaints.

Aggressive behaviour in childhood and adolescence: the role of smoking during pregnancy, evidence from four twin cohorts in the EU-ACTION consortium.

BACKGROUND: Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. METHODS: Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18. RESULTS: MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. CONCLUSIONS: Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour.

Associations between autistic-like traits and polymorphisms in NFKBIL1.

OBJECTIVE: The immune system has been suggested to be associated with neuropsychiatric disorders; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NF-κB) have been reported in individuals with autism spectrum disorder (ASD). The aim of this study was to investigate possible associations between autistic-like traits (ALTs) and single nucleotide polymorphisms (SNPs) in NFKB1 (encoding a subunit of the NF-κB protein complex) and NF-κB inhibitor-like protein 1 (NFKBIL1). METHODS: The study was conducted in a cohort from the general population: The Child and Adolescent Twin Study in Sweden (CATSS, n = 12 319, 9-12 years old). The subjects were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory. Five SNPs within the two genes were genotyped (NFKBIL1: rs2857605, rs2239707, rs2230365 and rs2071592; NFKB1: rs4648022). RESULTS: We found significant associations for two SNPs in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. Furthermore, we found nominal association in the case-control study for rs2230365, replicating earlier association between this SNP and ASD in an independent genome-wide association study. CONCLUSION: The shown associations between polymorphisms in NFKBIL1 and ALTs are supporting an influence of the immune system on neuropsychiatric symptoms.

The Autism-Tics, ADHD and other Comorbidities inventory (A-TAC): previous and predictive validity.

BACKGROUND: Reliable and easy to administer screening instruments focusing on neurodevelopmental disorders and associated conditions are scarce. The Autism-Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated and reporting good- excellent validity for several disorders. This article aims to expand these findings by including more conditions in a substantially larger sample augmented with the Swedish National Patient Register (NPR). METHODS: Since 2004 parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden, CATSS. The CATSS is linked to the NPR which includes data from in- and outpatient care. Data on neurodevelopmental disorders (A-TAC) collected in CATSS were compared with diagnoses from the NPR. We investigated diagnoses that had been made both before (previous validity) and after (predictive validity) the interview. RESULTS: Sensitivity and specificity of A-TAC scores for predicting earlier or later clinical diagnoses were mostly good-excellent, with values of the area under the curve for a clinical diagnosis of autism spectrum disorder (ASD) of .98, attention deficit hyperactivity disorder (ADHD) .93, learning disorder (LD) .92, and oppositional defiant disorder (ODD) .99, with small differences in terms of previous and predictive analyses. A-TAC provided little validity for eating disorders. CONCLUSION: The result support previous claims: A-TAC is a broad screening instrument with a particular strength in assessing ASD, ADHD, LD, and ODD at ages 9 and 12, and also provides phenotypic information about other child psychiatric disorders.

The protective effect of character maturity in child aggressive antisocial behavior.

BACKGROUND: Childhood aggressive antisocial behavior (CD) is one of the strongest predictors of mental health problems and criminal behavior in adulthood. The aims of this study were to describe personality profiles in children with CD, and to determine the strength of association between defined neurodevelopmental symptoms, dimensions of character maturity and CD. METHODS: A sample of 1886 children with a close to equal distribution of age (9 or 12) and gender, enriched for neurodevelopmental and psychiatric problems were selected from the nationwide Child and Adolescent Twin Study in Sweden. Their parents rated them according to the Junior Temperament and Character Inventory following a telephone interview during which information about the children's development and mental health was assessed with the Autism-Tics, AD/HD and other Comorbidities inventory. RESULT: Scores on the CD module significantly and positively correlated with scores on the Novelty Seeking temperament dimension and negatively with scores on character maturity (Self-Directedness and Cooperativeness). In the group of children with either neurodevelopmental or behavioral problems, the prevalence of low or very low character maturity was 50%, while when these two problems coexisted the prevalence of low or very low character maturity increased to 70%. Neurodevelopmental problems (such as: oppositional defiant disorder, symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder) and low scores on character maturity emerged as independently significant predictors of CD; in a multivariable model, only oppositional defiant symptoms and impulsivity significantly increased the risk for coexisting CD while a mature self-agency in a child (Self-Directedness) remained a significant protective factor. CONCLUSION: These results suggest that children's willpower, the capacity to achieve personally chosen goals may be an important protective factor - even in the presence of neurodevelopmental and psychiatric problems - against progressing into persistent negative outcomes, such as aggressive antisocial behaviors.

Mentally disordered offenders in Sweden: differentiating recidivists from non-recidivists in a 10-year follow-up study.

BACKGROUND: Forensic psychiatric patients present a challenge as they manifest severe mental disorders together with criminal behaviour. There are well-known risk factors for criminal behaviour in the general population, yet knowledge of what predicts reconviction in the Swedish forensic population in the long-term perspective is still insufficient. AIMS: The study aims to (1) describe background and clinical characteristics of forensic psychiatric patients in a 10-year follow-up, (2) analyse risk factors associated with recidivism, and (3) test the predictive validity of risk factors for general and violent criminality. METHODS: Detailed information on all offenders from the Malmö University Hospital catchment area sentenced to forensic psychiatric in-patient treatment from 1999-2005 (n = 125) was collected. Court decisions were collected up until the end of 2008 (median follow-up time = 6.2 years, range = 0.6-9.7 years). RESULTS: Relapse in general crime (n = 30) was predicted by low educational attainment, mental disorder in a first degree relative, and low age at first sentenced crime. Relapse in violent crime (n = 16) was predicted by low educational attainment and low GAF scores. Patients with a restriction order were less likely to relapse in both crime categories. CONCLUSIONS: Signs of childhood adversities together with early debut in criminality appeared as important risk factors for general and violent recidivism. Forensic psychiatric treatment combined with a restriction order was demonstrated as a protective factor against recidivism, suggesting that the risk of recidivism is strongly related to the level of supervision. Although the low number of recidivism cases is highly desirable, it unfortunately reduces the power of the analyses in this paper.

Examining and interpreting the female protective effect against autistic behavior.

Male preponderance in autistic behavioral impairment has been explained in terms of a hypothetical protective effect of female sex, yet little research has tested this hypothesis empirically. If females are protected, they should require greater etiologic load to manifest the same degree of impairment as males. The objective of this analysis was to examine whether greater familial etiologic load was associated with quantitative autistic impairments in females compared with males. Subjects included 3,842 dizygotic twin pairs from the Twins Early Development Study (TEDS) and 6,040 dizygotic twin pairs from the Child and Adolescent Twin Study of Sweden (CATSS). In both samples, we compared sibling autistic traits between female and male probands, who were identified as children scoring in the top 90th and 95th percentiles of the population autistic trait distributions. In both TEDS and CATSS, siblings of female probands above the 90th percentile had significantly more autistic impairments than the siblings of male probands above the 90th percentile. The siblings of female probands above the 90th percentile also had greater categorical recurrence risk in both TEDS and CATSS. Results were similar in probands above the 95th percentile. This finding, replicated across two nationally-representative samples, suggests that female sex protects girls from autistic impairments and that girls may require greater familial etiologic load to manifest the phenotype. It provides empirical support for the hypothesis of a female protective effect against autistic behavior and can be used to inform and interpret future gene finding efforts in autism spectrum disorders.

The genetic and environmental structure of the character sub-scales of the temperament and character inventory in adolescence.

BACKGROUND: The character higher order scales (self-directedness, cooperativeness, and self-transcendence) in the temperament and character inventory are important general measures of health and well-being [Mens Sana Monograph 11:16-24 (2013)]. Recent research has found suggestive evidence of common environmental influence on the development of these character traits during adolescence. The present article expands earlier research by focusing on the internal consistency and the etiology of traits measured by the lower order sub-scales of the character traits in adolescence. METHODS: The twin modeling analysis of 423 monozygotic pairs and 408 same sex dizygotic pairs estimated additive genetics (A), common environmental (C), and non-shared environmental (E) influences on twin resemblance. All twins were part of the on-going longitudinal Child and Adolescent Twin Study in Sweden (CATSS). RESULTS: The twin modeling analysis suggested a common environmental contribution for two out of five self-directedness sub-scales (0.14 and 0.23), for three out of five cooperativeness sub-scales (0.07-0.17), and for all three self-transcendence sub-scales (0.10-0.12). CONCLUSION: The genetic structure at the level of the character lower order sub-scales in adolescents shows that the proportion of the shared environmental component varies in the trait of self-directedness and in the trait of cooperativeness, while it is relatively stable across the components of self-transcendence. The presence of this unique shared environmental effect in adolescence has implications for understanding the relative importance of interventions and treatment strategies aimed at promoting overall maturation of character, mental health, and well-being during this period of the life span.

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.

Offenders in emerging adulthood: School maladjustment, childhood adversities, and prediction of aggressive antisocial behaviors.

Early psychosocial adversities and maladjustment, such as childhood maltreatment and school adjustment problems, have been linked to an increased risk of aggressive antisocial behaviors. Yet, clinical studies of subjects at the highest risk of persistence in such behaviors are rare, especially during the life-changing transition years of emerging adulthood. This study describes early predictors of aggressive antisocial behaviors in a large, nationally representative cohort of Swedish, male violent offenders in emerging adulthood (age range = 18-25 years; N = 270). First, data on psychosocial background characteristics and aggressive antisocial behaviors (including age at onset) are provided. Second, early predictors of aggressive antisocial behaviors are tested in bivariate and multivariate interactive models. The offenders demonstrated a diversity of early onset adversities and disruptive behaviors, in line with established risk factors for subsequent criminality and adverse outcomes in a variety of life domains. Severe school adjustment problems, especially bullying others and early onset truancy, were important and interrelated predictors of aggressive antisocial behaviors over the lifetime, whereas childhood adversities such as parental substance or alcohol abuse and repeated exposure to violence at home during childhood were interrelated predictors of aggressive antisocial behaviors, albeit with less statistical importance. The findings stress the importance of early identification of individuals in the risk zone of developing severe and persistent aggressive antisocial behaviors and of early preventive interventions directed toward families with high-risk profiles. The findings also provide initial guidelines on which psychosocial background risk factors that need to be considered first-hand in early interventions. (PsycINFO Database Record

Childhood attention-deficit/hyperactivity disorder symptoms and the development of adolescent alcohol problems: A prospective, population-based study of Swedish twins.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of problematic alcohol and other substance use in adolescence. This study used data from an ongoing, prospective, population-based twin study of Swedish children and adolescents to evaluate the extent to which the association between ADHD symptoms and alcohol problems reflects a unique source of genetic or environmental risk related to ADHD versus a broader predisposition to youth externalizing behavior. We used all available data from same-sex monozygotic (MZ) and dizygotic (DZ) twins on ADHD symptoms in childhood (age 9/12; N = 15,549) and alcohol problems in late adolescence (age 18; N = 2,564). Consistent with prior longitudinal studies, the phenotypic association between hyperactive/impulsive ADHD symptoms and alcohol problems was small in magnitude, whereas the association for inattentive symptoms was even weaker. Additive genetic influences explained 99.8% of the association between hyperactive/impulsive symptoms and alcohol problems. Furthermore, we found that the genetic risk specifically associated with hyperactive/impulsive symptoms was attenuated when estimated in the context of externalizing behavior liability during childhood, of which ADHD symptoms were specific expressions. In sensitivity analyses exploring hyperactivity in mid-adolescence, we found a similar pattern of genetic associations. These results are consistent with previous findings of genetically driven overlap in the etiology of ADHD and problematic alcohol use. At least some of this co-occurrence may result from a general predisposition to externalizing behaviors in youth. © 2015 Wiley Periodicals, Inc.

Birth weight as an independent predictor of ADHD symptoms: a within-twin pair analysis.

BACKGROUND: Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors. METHOD: Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM-IV inattentive and hyperactive-impulsive ADHD symptoms by the Autism - Tics, AD/HD and other Comorbidities (A-TAC) inventory (N = 21,775 twins). Birth weight was collected prospectively through the Medical Birth Registry. We used a within-twin pair design to control for genetic and shared environmental factors. RESULTS: Reduced birth weight was significantly associated with a mean increase in total ADHD (ß = -.42; 95% CI: -.53, -.30), inattentive (ß = -.26; 95% CI: -.33, -.19), and hyperactive-impulsive (ß = -.16; 95% CI: -.22, -.10) symptom severity. These results imply that a change of one kilogram of birth weight corresponded to parents rating their child nearly one unit higher (going from "no" to "yes, to some extent" on a given symptom) on the total ADHD scale. These associations remained within pairs of MZ and DZ twins, and were also present when restricting the analyses to full term births. CONCLUSIONS: There is an independent association between low birth weight and all forms of ADHD symptoms, even after controlling for all environmental and genetic confounds shared within twin pairs. These results indicate that fetal growth restriction (as reflected in birth weight differences within twin pairs) and/or the environmental factors which influence it is in the casual pathway leading to ADHD.

Autism spectrum disorders and coexisting disorders in a nationwide Swedish twin study.

BACKGROUND: Evidence from twin and molecular genetic studies is accumulating that Autism Spectrum Disorder (ASD) shares substantial etiological factors with other disorders. This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. METHODS: Parents of all Swedish 9-year-old twins born between 1992 and 2001 (n = 19,130) underwent a telephone interview designed to screen for child psychiatric disorders, including ASD. To ensure full coverage of child psychiatric disorders, data were also retrieved from population-based health registers. We investigated the coexistence of eight psychiatric disorders known to coexist with ASDs in probands and their co-twins. RESULTS: Half of the individuals with ASDs (50.3%) had four or more coexisting disorders and only 4% did not have any concomitant disorder. The 'healthy co-twin' in ASD discordant monozygotic twin pairs was very often (79% of boys and 50% of girls) affected by at least one non-ASD disorder. The corresponding figures for ASD discordant dizygotic twin pairs were significantly lower (46% of males and 30% of females). CONCLUSIONS: Detailed phenotypic descriptions including symptoms of problems associated with a wide range of child psychiatric disorders may aid in unraveling the genetic architecture of ASD and should guide the development of intervention strategies addressing each problem type specifically.

Experienced consequences of being diagnosed with ADHD as an adult - a qualitative study.

BACKGROUND: Despite increasing knowledge of attention deficit hyperactivity disorder (ADHD) across the life span, there is still little research on adults' own experiences of being diagnosed with ADHD. The aim of the present study was to explore and describe patients' experiences and perceptions of being diagnosed with ADHD in adulthood. The study can be seen as an attempt to validate the diagnosis from a patient perspective. METHODS: Twenty-one adults diagnosed with ADHD were individually interviewed. The interviews were open-ended and exploratory, analysed with a qualitative phenomenographical approach, and the results were described in categories. RESULTS: Positive experiences were dominant, but there was a complex intra- and inter-individual variation of experiences. Descriptions focused on the diagnosis, on identity, and on life. The diagnosis was described as explaining a previously inexplicable life history, but was also questioned, both as a phenomenon and in relation to the individual (the diagnosis in focus). It was experienced as providing self-knowledge and increased value, but could also cause devaluation and concern about identity (identity in focus). It meant help to achieve a better life, but was also perceived to restrict possibilities and cause disappointment over lack of professional help. It could lead to a wish for an earlier diagnosis that could have spared suffering, as well as to a changed view of the participants' relatives (life in focus). All but one of the interviewees expressed important positive consequences of being diagnosed with ADHD. About half of them acknowledged negative aspects of being diagnosed, but none regretted going through the neuropsychiatric evaluation. CONCLUSIONS: From a patient perspective, there are major positive consequences of being diagnosed with ADHD, compared to the undiagnosed situation. Knowledge of the individual's combination of experiences is important for professionals, as these experiences can affect well-being and interfere with treatment. Negative experiences in particular might need to be addressed in the treatment work.

Predictors of adolescents' consent to use health records for research and results from data collection in a Swedish twin cohort.

INTRODUCTION: Non-random selection into a study population due to differences between consenters and non-consenters may introduce participation bias. Past investigations of factors predicting consent to collection of medical health records for research imply that age, sex, health status, and education are of importance for participation, but disagree on the direction of effects. Very little is known about influences on consent from adolescents. METHODS: Two cohorts of Swedish 15-year-old twins (total n = 4,611) previously invited to the Child and Adolescent Twin Study in Sweden (CATSS) responded to a questionnaire with information on sex, individual's health, height, weight, and parental factors. The questionnaire included a question for consent to collection of medical health records. Predictors for consent were analyzed using logistic regression. Additionally, regional differences in the collection of health records of consenters were evaluated. RESULTS: Males were significantly less likely to consent compared to females (OR 0.74, 95% CI 0.64-0.85). The twin siblings' decision to consent was strongly associated with consent (OR 10.9, 95% CI 8.76-13.5), and individuals whose parents had responded to the original CATSS study were more likely to consent to record collection at age 15 (OR 2.2, 95% CI 1.81-2.75). Results of the subsequent collection of consenters' medical health records varied between geographical regions of Sweden. CONCLUSION: We identified several predictors for adolescents' consent to collection of their medical health records. Further selection was introduced through the subsequent record collection. Whether this will induce participation bias in future studies depends on the research questions' relationship to the identified predictors.

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Childhood neurodevelopmental problems and adolescent bully victimization: population-based, prospective twin study in Sweden.

Bully victimization is a common problem among children with neurodevelopmental disorders, including attention deficit/hyperactivity disorder and autism spectrum disorder. Previous research was mostly cross-sectional and seldom accounted for co-morbid psychopathology, which makes it difficult to draw conclusions about causality and specificity of any association. Using a genetically informative prospective design, we investigated the association between various neurodevelopmental problems (NDPs) in childhood and bully victimization in adolescence, and the relative contributions of genetic and environmental factors to this association. We obtained parent-reports of NDPs at age 9/12 years and self-reported bully victimization at age 15 for 3,921 children participating in the The Child and Adolescent Twin Study in Sweden (CATSS). Structural equation modelling was used to control for NDP co-morbidity and bully victimization at baseline. Cholesky decomposition was used to analyse genetic and environmental contributions to observed associations. Because most of the NDPs were associated to later bully victimization, a common effect of all NDPs was summarized into a general NDP factor. Controlling for this general factor, only problems with social interaction and motor control uniquely predicted subsequent bully victimization in girls. General and unique associations were influenced by both genetic and unique environmental factors. NDPs in general and social interaction and motor problems in particular predicted later bully victimization. The longitudinal design and twin analyses indicated that these associations might be causal. Knowledge of these vulnerabilities may be important when designing risk assessment and prevention strategies.

Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity.

Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3 h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid ß (Aß42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p = 0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aß42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.

Exposure to air pollution from traffic and neurodevelopmental disorders in Swedish twins.

BACKGROUND: Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated. AIM: We aimed to explore the risk for autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) among children in relation to pre- and postnatal exposure to air pollution from road traffic. METHODS: Parents of 3,426 twins born in Stockholm during 1992-2000 were interviewed, when their children were 9 or 12 years old, for symptoms of neurodevelopmental disorders. Residence time-weighted concentrations of particulate matter with a diameter <10 µm (PM10) and nitrogen oxides (NOx) from road traffic were estimated at participants' addresses during pregnancy, the first year, and the ninth year of life using dispersion modeling, controlling for seasonal variation. Multivariate regression models were used to examine the association between air pollution exposure and neurodevelopmental outcomes, adjusting for potential confounding factors. RESULTS: No clear or consistent associations were found between air pollution exposure during any of the three time windows and any of the neurodevelopmental outcomes. For example, a 5-95% difference in exposure to NOx during pregnancy was associated with odds ratios (ORs) of 0.92 (95% confidence interval (CI): 0.44-1.96) and 0.90 (95% CI: 0.58-1.40) for ASD and ADHD respectively. A corresponding range in exposure to PM10 during pregnancy was related to ORs of 1.01 (95% CI: 0.52-1.96) and 1.00 (95% CI: 0.68-1.47) for ASD and ADHD. CONCLUSIONS: Our data do not provide support for an association between pre- or postnatal exposure to air pollution from road traffic and neurodevelopmental disorders in children.